Ulcerative colitis （UC）， a chronic relapsing inflammatory bowel disease， involves multifaceted pathological mechanisms such as intestinal barrier dysfunction， immune dysregulation， and oxidative stress. Current therapeutic strategies remain limited in efficacy and safety. In recent years， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway has emerged as a pivotal therapeutic target for UC due to its central role in energy metabolism， inflammatory regulation， and intestinal homeostasis. This article systematically reviewed the mechanisms by which traditional Chinese medicine （TCM） prevented and treated UC through the regulation of the AMPK signaling pathway， with a focus on elucidating AMPK's multidimensional regulatory network in inflammatory signaling crosstalk， alleviating oxidative stress， restoring intestinal immune balance， repairing the intestinal barrier， and modulating gut microbiota. Leveraging its unique advantages of multi-target engagement and low toxicity， TCM demonstrates promising potential in UC treatment and has become a focal area of research. By systematically summarizing and synthesizing the existing literature on TCM-mediated AMPK pathway modulation in UC， this review aims to provide a theoretical foundation for advancing mechanistic research and clinical interventions in UC.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Breast cancer is one of the most common and fatal malignancies among women worldwide, and its treatment efficacy is often limited by drug resistance and the presence of undruggable targets. Traditional small-molecule drugs have difficulty effectively modulating certain critical targets such as transcription factors and non-coding RNAs, necessitating new therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) function by recruiting pathogenic proteins to the cellular ubiquitin-proteasome system, thereby inducing their specific degradation. In contrast, ribonuclease-targeting chimeras (RIBOTACs) utilize small-molecule ligands but bind to RNA and direct endogenous RNases to selectively degrade pathogenic RNA molecules. By employing a "degradation rather than inhibition" mechanism, targeting chimera technology broadens the druggable landscape and offers a novel precision therapeutic strategy for breast cancer, particularly for refractory and drug-resistant cases. This approach not only overcomes the limitations of traditional drugs, such as the absence of suitable binding sites or poor selectivity, but also reduces required dosages and potential adverse effects. Recent studies have preliminarily demonstrated the therapeutic potential of PROTACs and RIBOTACs in breast cancer, encompassing target design, mechanistic investigation, and preclinical as well as early clinical applications. Research into these technologies reveals their ability to tackle previously undruggable targets, thereby providing theoretical support for the development of safer and more effective precision therapies for breast cancer. In the future, with advances in drug delivery systems and clinical trials, PROTACs and RIBOTACs are expected to be used synergistically with immunotherapy and chemotherapy, offering breast cancer patients more promising comprehensive treatment options and potentially driving oncology toward broader intervention of undruggable targets.
Humans ; Breast Neoplasms/drug therapy* ; Female ; Proteolysis ; Ribonucleases/metabolism* ; Molecular Targeted Therapy/methods* ; Antineoplastic Agents/therapeutic use*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective:To evaluatethe therapeutic efficacy and underlying mechanism of sodium houttuyfonate in treating airway inflammation in allergic asthma induced by co-exposure to the environmental pollutant benzo[a] pyrene (BaP) and ovalbumin (OVA).Methods:Thirty BALB/c mice were randomly divided into five groups with six mice in each group using a block randomization method: control, BaP, asthma model (OVA), BaP-exacerbated asthma (BaP+ OVA), and sodium houttuyfonate-treated BaP-exacerbated asthma (BaP+ OVA+ SH) groups. A mouse model of exacerbated asthma induced by co-exposure to BaP and OVA was established. Airway hyperresponsiveness, leukocyte distribution in bronchoalveolar lavage fluid (BALF), expression of cytokines such as IL-4, IL-13, IL-25, IL-33, thymic stromal lymphopoietin (TSLP) and IFN-γ, serum OVA-specific antibodies (IgE, IgG2a and IgG1), levels of malondialdehyde and superoxide dismutase (SOD) in lung tissues, and histopathological changes in lung tissues were evaluated. Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of suppression of tumorigenicity 2 (ST2), extracellular regulated protein kinases (ERK), and phosphorylated ERK (p-ERK). Statistical analysis was conducted using analysis of variance and other statistical methods.Results:Compared with the BaP+ OVA group, the mice in the BaP+ OVA+ SH group showed significantly reduced airway hyperresponsiveness ( P<0.01), decreased numbers of total leukocytes ( P<0.01), neutrophils ( P<0.05), and lymphocytes ( P<0.01) in BALF, significantly downregulated secretion of IL-4, IL-13, IL-25, IL-33 and TSLP ( P<0.01), and inhibited production of IgE ( P<0.01) and IgG1 ( P<0.05). Additionally, sodium houttuyfonate treatment significantly decreased the malondialdehyde levels in lung tissues of mice with BaP-exacerbated asthma ( P<0.05) and reduced airway inflammatory cell infiltration, mucus secretion, and collagen fiber proliferation. Sodium houttuyfonate could supress the expression of ST2 and ERK ( P<0.05), inhibit ERK phosphorylation ( P<0.01), alleviate oxidative stress injury, and reduce collagen fiber proliferation in mouse lung tissues, thereby blocking the progression of BaP-exacerbated asthmatic inflammation. Conclusions:BaP exacerbates OVA-sensitized asthmatic airway inflammation in mice by inducing airway remodeling through the IL-33-ST2/ERK pathway. Sodium houttuyfonate inhibits this pathway, thereby preventing the progression of BaP-exacerbated asthma inflammation. This study provides new insights into the prevention and treatment of different phenotypes of asthma.

Objective:To investigate the relationship between collateral circulation and viable myocardium (VM) in patients with coronary chronic total occlusion (CTO).Methods:A total of 88 patients (76 males, 12 females, age (61.0±9.8) years) with coronary CTO were retrospectively analyzed. All patients underwent both 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT myocardial perfusion imaging and 18F-FDG PET myocardial metabolism imaging for evaluation of VM at the First People′s Hospital of Changzhou between September 2012 and June 2023, and they were scheduled to receive coronary revascularization. The perfusion/metabolism mismatch myocardium was regarded as VM. The VM index within the CTO region was calculated, reflected the quantities of VM: VM index=(summed rest score within the CTO region-summed 18F-FDG uptake score within the CTO region)/reduced perfusion myocardial segments×4×100%. Rentrop grading of collateral circulation was performed based on coronary angiography. The differences of VM index within the CTO region between poor-developed (PD, Rentrop grade 0-1) and well-developed (WD, Rentrop grade 2-3) collateral circulation, and among different Rentrop grades were analyzed by the independent-sample t test or Kruskal-Wallis rank sum test. The linear regression analysis was used to evaluate the relationship between Rentrop grading and VM index within the CTO region. The ROC curve was constructed to analyze the predictive value of Rentrop grading for VM within the CTO region. Results:The VM index within the CTO region was significantly higher in WD patients ( n=54) compared to those in PD patients ( n=34): (45.8±16.3)% vs (21.3±16.7)% ( t=-6.79, P<0.001). Moreover, the VM index within the CTO region increased with increased Rentrop grade, and there was a significant difference among 4 groups ( H=30.22, P<0.001). Multiple linear regression analysis showed that only the Rentrop grading was an independent influencing factor for the VM index within the CTO region ( β=9.29, 95% CI: 5.91-12.67, P<0.001). ROC curve showed that the sensitivity and specificity of Rentrop grading score≥2 for predicting the presence or absence of VM within the CTO region were 65.8%(52/79) and 7/9, with the AUC of 0.724(95% CI: 0.619-0.814). Conclusions:In CTO patients who are scheduled for revascularization and evaluation of VM, as the Rentrop grading increases, the VM index within the CTO region also increases. The presence of VM within the CTO region can be predicted with Rentrop grading score ≥2.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

Objective:To understand the evolution and variation characteristics of the H1N1 influenza virus in Wuxi City from 2018 to 2023.Methods:Real time PCR was used to perform nucleic acid testing on throat swab samples of influenza like cases sent to sentinel hospitals for testing. The influenza A (H1N1) pdm09 positive samples were subjected to cell culture, and nucleic acid was extracted from strains with a red blood cell agglutination test (HA) ≥1∶8. The whole genome sequence was amplified, and a library was constructed. The MiSeq sequencer was used for sequencing on the machine. Using NC_026431.1 as a reference strain, we analyzed the offline data using CLC Genomics Workbench (Version 23) software. MEGA 7.0 software was used to construct a phylogenetic tree, and NetNGlyc 1.0 Server software was used to predict N-glycosylation sites.Results:The nucleotide and amino acid homology between 38 strains of A (H1N1) pdm09 influenza virus from 2018 to 2023 were 96.06%-100% and 96.12%-100%, respectively. From February to May 2023, all 12 strains of A (H1N1) pdm09 had two amino acid mutation sites occurring in the HA antigenic determinant cluster, namely the Ca region (A203T) and the Cb region (K71Q). No mutations were found in the HA receptor binding site and NA resistance site. The strains from January to June 2018 belong to the 6B. 1A evolutionary branch, the strains from December 2018 to January 2020 belong to three evolutionary branches: 6B. 1A. 1, 6B. 1A. 5a, and 6B. 1A. 7, and the strains from February to May 2023 belong to the 6B. 1A. 5a. 2a evolutionary branch. 38 strains of A (H1N1) pdm09 HA gene all have 7 potential N-glycosylation sites, while NA gene has 7-8 potential N-glycosylation sites.Conclusions:There are characteristic amino acid mutation sites of H1N1 influenza A in Wuxi City from 2018 to 2023. The emergence of these mutation sites may affect the virus′s transmission and antigenic changes.

Objective:To observe the changes of retinal and choroidal blood flow density and thickness in macula of different myopic dioptre eyes, and to analyze the correlation between retinal and choroidal blood flow density and axial length (AL).Methods:A retrospective clinical study. From October 2022 to May 2023, 86 eyes of 56 myopic patients scheduled for refractive surgery in Department of Ophthalmology, PLA Central Theater CommandGeneral were included into the study. According to the equivalent spherical specular degree (SE), 19, 21, 27 and 19 eyes of low myopia group (group A), moderate myopia group (group B), high myopia group (group C) and super high myopia group (group D) were observed. Optical coherence tomography angiography (OCTA) and AL measurement were performed in all patients. The diopter was expressed in SE. AL was measured by ultrasonic bio-meter. OCTA scanner was used to scan the macular region in the range of 3 mm × 3 mm. The software automatically divided the macular region into two concentric circles with the fovea as the center, which were 1 mm in diameter respectively, the paracentric fovea of 1-3 mm was divided into 5 regions: superior, nasal, inferior and temporal. The superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal capillary plexus (CC), choroidal blood flow density, retinal and choroidal thickness were measured. The correlation between AL and blood flow density and thickness was analyzed by Pearson correlation analysis.Results:There was no significant difference in SCP blood density and DCP blood density in the fovea in groups A, B, C and D ( P>0.05) .There were significant differences in DCP flow density among superior, nasal, inferior and temporal areas ( P<0.05), the difference was significant ( P<0.05). There was no significant difference in the fovea area between the four groups ( P>0.05), but there was significant difference in the superior, nasal, inferior and temporal areas ( P<0.05). Different macular regions: there were statistically significant among group A, group B, and group C, group D ( P<0.05). Results of correlation analysis, AL was negatively correlated with DCP blood flow density ( r=-0.504, -0.500, -0.460, -0.465), retinal thickness ( r=-0.348, -0.338, -0.312, -0.230), macular subarea CC ( r=-0.633, -0.666, -0.667, -0.710, -6.82), choroidal layer ( r=-0.635, -0.687, -0.659, -0.703, -0.680) and choroidal thickness ( r=-0.665, -0.605, -0.656, -0.648,-0.643) ( P<0.05). Conclusions:AL is negatively correlated with DCP, CC, CDF, retinal and choroidal thickness in the eyes with myopia. SCP, DCP and retinal thickness in fovea did not change significantly, and temporal choroidal thickness changed earlier than other areas.